Can Dietary Changes Improve Epilepsy Outcomes?

Treatments for epilepsy have come a long way since the use of fasting dating back to 500 BC. Neurologists started using the ketogenic diet (KD) to treat seizures as early as the 1920s; however, with the development of modern anticonvulsant medications, people lost interest. Between 20% and 30% of persons with epilepsy are refractory to medications. Thus KD and other dietary therapies, such as the modified Atkins diet (MAD), have returned to the spotlight as viable nonpharmacological treatment options for medication refractory epilepsy.1

Dietary therapies

The ketogenic diet is a high-fat diet, which is described as ratios of grams of fat to grams of non-fat (protein and carbohydrates) foods, typically 3:1 or 4:1. The ratio of the MAD is 0.9:1, providing approximately 60% of calories from fat, 30% from protein (higher than the KD and “normal” diet), and 10% from carbohydrates (higher than the KD). The consensus statement published in 2009 by the International Ketogenic Diet Study Group recommends “KD should be strongly considered in a child who has failed 2 to 3 anticonvulsant therapies, regardless of age or gender, and particularly in those with symptomatic generalized epilepsies.”2

A Cochrane Review in 2016 yielded 7 randomized controlled trials. The variables of interest were heterogeneous: one trial compared 3:1 and 4:1 ratios of the KD; another compared 2.5:1 and 4:1 ratios. Another trial compared KD versus regular diet, and then classical KD with KD utilizing medium-chain triglycerides as the source of fat. One trial compared fasting versus gradual initiation of the KD. One trial compared MAD with 10 versus 20 grams of carbohydrates per day. Another trial compared MAD, KD, and regular diet, while one trial compared MAD to regular diet. Taken together, all showed that at least 38% of patients had more than a 50% decrease in seizures at 3 months, with the benefit maintained at 1 year. The rate of seizure freedom on KD reached 55% in the 4:1 ratio after 3 months, and 10% in the MAD.3

There have been several publications supporting the particular efficacy of KD in certain epilepsy syndromes and causes, including myoclonic-astatic epilepsy (Doose syndrome), severe myoclonic epilepsy of infancy (Dravet syndrome), tuberous sclerosis, infantile spasms, and Rett syndrome. Formula-feeding through tube or bottle would also be a favorable factor, as it would simplify food preparation and minimize chances of intolerance.

Based on specific metabolic abnormalities, there are 2 conditions in which the KD could be considered treatment of choice, to be used before 2 or 3 antiseizure medications have failed. Those are glucose transporter deficiency syndrome, in which glucose transport across the blood-brain barrier is impaired, and pyruvate dehydrogenase deficiency in which pyruvate cannot be metabolized into acetyl-coA.2 Moreover, findings suggest that other etiologies may benefit from dietary therapy, including genetic generalized epilepsies such as juvenile myoclonic and absence epilepsy, and epilepsies that are often considered catastrophic, including those due to malformations such as lissencephaly, hypoxic-ischemic injury, migrating focal seizures of infancy, and febrile infection-related epilepsy syndrome.4

Dietary therapies should be administered under the supervision of a program with particular expertise to allow for discussion of most appropriate dietary options, monitoring of short- and long-term adverse effects, and support of the patient and family through a change in lifestyle. The team’s essential providers are dietitian and physician (neurologist), however the team may also include a nurse, a nurse practitioner, a social worker, and an authorization specialist.

Complications during initiation of the diet may include vomiting, dehydration, hypoglycemia, and excessive acidosis. Use of carbonic anhydrase inhibitors such as topiramate and zonisamide increases the likelihood of acidosis. Constipation is a frequent adverse effect, which is treated by increasing hydration, giving foods such as avocado, or using laxatives.

Dr Kao is Attending Neurologist and Director of the Dietary Therapies Clinic of the Comprehensive Pediatric Epilepsy Program,Center for Neurosciences and Behavioral Medicine, Children’s National Medical Center, Washington, DC; Ms Cines is a Registered Dietician at Children’s National Medical Center; she specializes in gastrointestinal diseases and ketogenic diets.